The purpose of this project is to identify and characterize the mechanisms which enable the pore cells of the marine prosobranch gastropod Littorina littorea to specifically accumulate Cu in preference to other bioavailable metals. A series of experiments have been designed to demonstrate that these cells accumulate metals from the blood and to test if the observed selectivity shown by the cells in vivo is due to: (1) intrinsic properties unique to this particular cell type; (2) the activities of other cell types such as the basophil cells in the removal of metals other than Cu from the blood; (3) humoral factors which bind to Cu and act to both vector the metal to the cell and facilitate its uptake. A number of techniques including cell culture, energy dispersive X-ray microanalysis, radiometric analysis, gel electrophoresis, size exclusion high performance liquid chromatography and inductively coupled plasma mass spectrometry will be used to resolve the relative importance of the three factors outlined above. Short term kinetic studies will also be undertaken to determine if Cu uptake by the cells is carrier mediated. Competitive inhibition studies with other metals will be used to determine the specificity of the uptake system and the energetic requirements of the transport system will also be studied using various metabolic inhibitors. In combination, these studies will provide a mechanistic understanding of the processes which permit the sequential recognition, selection and vectoring of metals to specific cell types in higher eukaryotes. In the long term, these studies will also help in the development of Cu based molluscicides to control the spread of schistosomiasis by the gastropod Biomphalaria glabrata. Finally, these studies represent the first attempt to study the flux and turnover of Cu in cells quantitatively using stable isotopic analysis of 63Cu by inductively coupled plasma mass spectrometry. This technique therefore offers a new methodology to the health related sciences for the study of this essential, but potentially toxic element.